Define initiating, modulating and effector cellular and humoral lymphoid cell immunologic responses to neural antigen sensitization leading to experimental allergic encephalomyelitis (EAE) in rats and other animals hosts. Processing of myelin basic protein (MBP) by macrophages with presentation of the processed MBP to and activation of initiating T cells, the identify of those circulating endogenous MBP fragments that appear to exert an important immunoinhibitory influence on MBP-reactive and potentially injurious clones of lymphoid cells, and mechanism(s) whereby B cells in conjunction with activation of the clotting cascade cause clinical manifestations of disease and contribute to myelin injury will receive particular emphasis in this work. Extension of our findings concerning EAE in animals to patients with multiple sclerosis (MS) will include similarly identifying crucial circulating immunoinhibiting MBF fragments which disappear in the sera of patients in association with acute exacerbations of disease and launching efforts to transfer some component of the MS process to an animal host using peripheral blood mononuclear cells or plasma of selected MS patients. Our long term goal is devising efficacious, safe and specific therapeutic modalities decreasing the frequency of or entirely preventing clinical relapses of MS and/or prolonging clinical remissions when they occur, in continuing efforts to decrease the magnitude of impact of this devastating chronic neurologic health problem.